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Patients treated with izalontamab brengitecan (iza-bren; BL-B01D1) had superior overall response rate (ORR) compared with chemotherapy in patients with recurrent or metastatic nasopharyngeal carcinoma (NPC), according to results from the BL-B01D1-301 study (NCT06118333) presented at the 2025 European Society for Medical Oncology (ESMO) Congress and published in The Lancet.^1,2

The ORR by blinded independent central review was 54.6% (95% CI, 45.2%–63.8%) with iza-bren vs 27.0% (95% CI, 19.1%–36.0%) with chemotherapy, with an odds ratio of 3.3 (95% CI, 1.9–5.8; P < .0001) showing it was significantly higher in this primary end point.¹

“This was the first randomized phase 3 study evaluating iza-bren in recurrent or metastatic NPC. Our study has met its primary end point for ORR, and we can see a clinically meaningful improvement in progression-free survival [PFS] and it has a management safety profile,” said Huaqiang Zhou, MD, of Sun Yat-sen University Cancer Center in Guangzhou, China, in his presentation.¹

Approximately 20% to 30% of patients with NPC have recurrent or distant metastases, and current treatment options have low response rates. Iza-bren is a potentially first-in-class topoisomerase 1 inhibitor-based EGFR and HER3 bispecific antibody-drug conjugate (ADC).

The multicenter, randomized, open-label, phase 3 BL-B01D1-301 trial was designed to investigate this agent in patients who had previously received at least 2 lines of systemic chemotherapy including at least 1 platinum-containing regimen and a PD-1 or PD-L1 inhibitor. The primary end points were ORR and overall survival (OS), with secondary end points including progression-free survival, duration of response (DOR), and safety.

Patients were enrolled in 55 hospitals in China. They were stratified by number of prior lines of platinum-based treatment, ECOG performance status of 0 vs 1, and presence/absence of liver metastases.

Of 522 patients who were screened, 386 were randomly assigned on a 1:1 basis with 191 receiving 2.5 mg/kg iza-bren on days 1 and 8 of a 3-week cycle with 195 receiving physician’s choice of chemotherapy.¹

The median age of patients was 50.0 in the treatment arm and 49.0 in the chemotherapy arm, with the majority being male in each arm (85.3% and 81.0%, respectively). The majority had ECOG performance status of 1 (75.9% in both arms). Over half of patients in both arms had received 2 prior lines of therapy with the rest having received at least 3 lines. The majority had received 2 prior lines of chemotherapy, with 48.2% of each arm having received 2 prior lines of platinum-based chemotherapy. Prior radiotherapy had been used in 89.5% of the experimental arm and 88.2% of the control arm.

Metastases were present at baseline in the liver, bones, and lungs in 47.6%, 49.2%, and 46.6% of the experimental arm and 48.7%, 46.7%, and 37.4% of the control arm.

Results were reported at median follow-up of 7.66 months for iza-bren and 7.10 months for chemotherapy. There was 1 complete response in the iza-bren arm and none in the control arm. The disease control rate was 82.4% with iza-bren vs 69.6% with chemotherapy. All subgroups favored iza-bren in this analysis.

The median DOR was 8.5 months for iza-bren vs 4.8 months for physician’s choice of chemotherapy (HR, 0.43; 95% CI, 0.22–0.83). The median PFS was 8.38 months with iza-bren vs 4.34 months for chemotherapy (HR, 0.44; 95% CI, 0.32–0.62), and this trend was consistent across subgroups. At this time, OS was not mature.

Treatment-related adverse events (TRAEs) of grade 3 or higher were reported in 79.9% of patients receiving iza-bren vs 61.6% of those receiving chemotherapy. Serious TRAEs occurred in 43.4% of patients in the iza-bren arm vs 27.0% in the chemotherapy arm, and 4 (2%) treatment-related deaths occurred in the iza-bren group. Dose reductions due to TRAEs were needed in 41.8% with iza-bren vs 24.3% with chemotherapy, and TRAEs leading to dose interruption occurred in 61.4% vs 18.4%, respectively. TRAEs led to treatment discontinuation in 2.6% vs 3.2%, respectively.

Hematological AEs were reported more frequently with iza-bren vs chemotherapy including anemia in 50% vs 10% and decreased platelet count in 43% vs 7%. Decreased white blood cell count occurred in 43% vs 44% and decreased neutrophil count occurred in 38% vs 41%, respectively. According to Zhou, these were well managed by standard supportive care. The majority of nonhematologic TRAEs were grade 1 or 2, and no new safety signals were identified.

Two cases of grade 2 interstitial lung disease (ILD) occurred in the experimental arm and 2 cases of grade 3 ILD occurred in the chemotherapy arm.

“Based on this trial, iza-bren represents a potential new standard of care for heavily pretreated patients with recurrent or metastatic NPC,” concluded Zhou.

REFERENCES:

1. Yang Y, Zhou H, Tang L, et al. Iza-bren (BL-B01D1), an EGFR×HER3 bispecific antibody-drug conjugate, versus physician’s choice of chemotherapy in heavily pretreated recurrent/metastatic nasopharyngeal carcinoma: a randomized, open-label, multicenter, phase III, pivotal study (BL-B01D1-303). Presented at: 2025 European Society for Medical Oncology Congress; October 17-21, 2025; Berlin, Germany. Abstract LBA35.

2. Yang Y, Zhou H, Tang L, et al. Izalontamab brengitecan, an EGFR and HER3 bispecific antibody–drug conjugate, versus chemotherapy in heavily pretreated recurrent or metastatic nasopharyngeal carcinoma: a multicentre, randomised, open-label, phase 3 study in China. Lancet. Published online October 19, 2025. doi:10.1016/S0140-6736(25)01954-3

Trodelvy (sacituzumab govitecan) led to a 51% reduction in the risk of progression or death compared with chemotherapy in patients with nonsquamous epidermal growth factor receptor–mutated non–small cell lung cancer that developed epidermal growth factor receptor tyrosine kinase inhibitor resistance, according to phase 3 results of the OptiTROP-Lung04 study presented during the European Society of Medical Oncology Congress 2025.

Results showed that, at a median follow-up of 18.9 months, the median progression-free survival assessed by blinded independent central review was 8.3 months with Trodelvy and 4.3 months with chemotherapy. The 12-month progression-free survival rates were 32% and 8%, respectively. The benefit with Trodelvy was observed across all prespecified subgroups.

The investigator-assessed median progression-free survival was 8.4 months with Trodelvy and 4.8 months with chemotherapy. The 12-month rates were 35% and 11%, respectively.

“Trodelvy demonstrated statistically significant and clinically meaningful improvements in progression-free and overall survival compared to platinum-based chemotherapy,” lead study author Dr. Li Zhang, professor of medical oncology at Sun Yat-sen University Cancer Center in Guangzhou, China, said in an oral presentation of the data. “The results of the OptiTROP-Lung04 study support Trodelvy as a promising new treatment option for patients with EGFR-mutated non–small cell lung cancer with epidermal growth factor receptor tyrosine kinase inhibitor resistance.”

Trodelvy is a TROP2 antibody-drug conjugate with a unique biofunctional linker that maximizes delivery of a belotecan-derivative topoisomerase I inhibitor payload to tumor cells. TROP2 is highly expressed in patients with EGFR-mutated non–small cell lung cancer, and preclinical data have shown that Trodelvy internalization and uptake are enhanced by EGFR mutations.

Current standard options for patients who relapse on third-generation EGFR tyrosine kinase inhibitors remain platinum-based chemotherapy, but more options are needed.

In the multicenter, open-label, phase 3 OptiTROP-Lung04 trial, 376 patients with nonsquamous stage 3B/3C or 4 non–small cell lung cancer with EGFR-sensitive mutations were randomly assigned 1:1 to receive Trodelvy at five milligrams per kilogram intravenously every two weeks or Alimta at 500 milligrams per square meter plus carboplatin area under the curve 5 or cisplatin at 75 milligrams per square meter every three weeks for up to four cycles, followed by Alimta maintenance at 500 milligrams per square meter every three weeks. Treatment was given until disease progression, intolerable toxicity, or patient request to discontinue therapy.

To be eligible for enrollment, patients needed to have an Eastern Cooperative Oncology Group performance status of zero or one and progression after third-generation tyrosine kinase inhibitor therapy or progression after first- or second-generation tyrosine kinase inhibitors with T790M-negative mutations.

Stratification factors included prior EGFR tyrosine kinase inhibitor therapy (third-generation in frontline versus second line versus no third-generation) or brain metastases (yes versus no).

The primary end point was progression-free survival assessed by blinded independent central review; secondary end points were overall survival, investigator-assessed progression-free survival, objective response rate, disease control rate, duration of response, and safety.

A total 148 patients on Trodelvy discontinued treatment due to disease progression (125 patients), patient or guardian withdrawal (12 patients), death (6 patients), side effects (2 patients), or other (3 patients). In the chemotherapy arm, 179 patients discontinued treatment due to disease progression (140 patients), patient/guardian withdrawal (16 patients), death (9 patients), side effects (5 patients), protocol deviation (2 patients), or other (7 patients). A total 69 and 102 patients in each arm, respectively, discontinued from the study due to death (67 and 101 patients) or were lost to follow-up (2 and 1 patients).

Patient baseline characteristics were generally well balanced between the Trodelvy (188 patients) and chemotherapy arms (188 patients). The median age was 60 years and 59 years, and 31% and 27% were at least 65 years. Most had a performance status of 1 (81% and 77%), had no smoking history (77% and 72%), had stage 4 disease (97% and 98%), and at least three metastatic sites (68% and 67%). A total 18% and 19% had brain metastases, and 13% and 18% had liver metastases. The majority in each arm had exon 19 deletions (56% and 63%), had unknown T790M mutation status (59% and 60%), and received a prior third-generation EGFR tyrosine kinase inhibitor in the frontline setting (63% and 62%).

The interim analysis showed that for Trodelvy, the median overall survival was not reached compared with 17.4 months with chemotherapy, leading to a 40% reduction in the risk of death. The 18-month overall survival rates were 66% and 48%, respectively. Overall survival was improved with Trodelvy across all prespecified subgroups.

Dr. Zhang also reported on subsequent anticancer treatment from the trial; 72% of patients on Trodelvy and 86% of those on chemotherapy received at least one subsequent treatment. In the Trodelvy and chemotherapy groups, respectively, these included chemotherapy (42%; 54%), specifically Alimta-based chemotherapy (37%; 13%), an EGFR tyrosine kinase inhibitor (43%; 40%), an anti-angiogenic agent (35%; 48%), immunotherapy (17%; 25%), or an antibody-drug conjugate (1%; 20%).

When assessed via blinded independent central review, the objective response rate with Trodelvy was 61% compared with 43% with chemotherapy; the disease control rate was 87% and 80%, respectively. The median duration of response was 8.3 months with Trodelvy and 4.2 months with chemotherapy; the 12-month rates were 36% versus 8%, respectively.

Regarding safety, treatment-related side effects occurred in 100% and 98% of Trodelvy– and chemotherapy-treated patients, respectively. Grade 3 or higher side effects occurred in 58% and 54% of patients, and serious side effects occurred in 9% and 18% of patients, respectively. Side effects that led to dose reductions and interruptions occurred in 30% and 37% of patients on Trodelvy; there were no side effects that led to discontinuation or death. In the chemotherapy arm, these rates were 23% and 33%; one patient each experienced side effects leading to discontinuation or death.

The median duration of exposure was 9.6 months with Trodelvy and 4.9 months with chemotherapy. The most common side effects in both arms were hematologic; Trodelvy had higher incidence of stomatitis that were mostly grade 1 or 2 (any-grade 62%; grade ≥3 5%). Ocular surface toxicities also occurred in 10% of patients on Trodelvy, all grade 1 or 2. No cases of interstitial lung disease or pneumonitis were reported on the Trodelvy arm.

Phase 3 trials are currently exploring Trodelvy alone and in combination with Tagrisso in patients with EGFR-mutant non–small cell lung cancer.

References

1. “Sacituzumab tirumotecan versus platinum-based chemotherapy in EGFR-mutated non-small cell lung cancer following progression on EGFR-TKIs” by Dr. Zhang, et al., presented at the 2025 ESMO Congress.
2. “Sacituzumab tirumotecan in advanced non-small-cell lung cancer with or without EGFR mutations” by Dr. Zhao, et al., Nat Med.

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